Energy minimization calculations and quantum mechanical computations on compounds of biological and pharmacological interest continue to give insight into and explanations of their modes of behavior, resulting in clues to their pharmacophores. The inhibition of the enzyme, aldose reductase, by a wide variety of compounds continues under investigation by QSAR techniques as well as by energy minimization computations, quantum mechanics and stereochemical considerations. A model for the interaction of a wide range of types of compounds with aldose reductase has been proposed and their common features attained. Preliminary circular dichroism studies on the enzyme itself seem to indicate the enzyme to be an Alpha protein.